The larynx has a challenging dual role in the simultaneous regulation of breathing for blood-gas homeostasis and voice production for communication. Particular challenges arise when the larynx is required to alter upper airway resistance to meet respiratory demands in a way that conflicts with requirements for voice production. This challenge is particularly for relevant the estimated 25% of the US population who experience respiratory abnormalities and also use the larynx for oral communication [1-16] Unfortunately, the vast majority of studies in respiratory physiology fail to appreciate the overla of laryngeal function in voice production, just as most studies in phonatory physiology fail to consider the lower airway's responsibility for blood-gas exchange. In fact, the larynx has the unique role of sustaining blood-gas homeostasis via regulation of the flow of gases into and out of the lungs as well as establishing resistance required for vocal fold vibration in voiced communication. Little if anything is known about reciprocal relations between these functions, particularly under conditions of respiratory abnormality that affect large sectors of the population. The primary objective of the current proposal is to address this gap by assessing the effects of varying concentrations of arterial carbon dioxide on laryngeal function during phonation. The secondary objective is to assess the inverse function, and that is the effects of laryngeal adjustments during phonation and rest on arterial carbon dioxide levels. The proposed work utilizes an interdisciplinary approach to address two specific aims in a single within-subjects experiment: (SA1) assess spontaneous fluctuations in phonatory laryngeal resistance during states of (a) induced hypocapnia (low arterial carbon dioxide) and (b) induced hypercapnia (high arterial carbon dioxide), in comparison to a control condition and (SA2) investigate reciprocal effects of laryngeal resistance modulations on respiratory homeostasis. The overarching hypothesis is that under conditions in which respiratory and phonatory demands conflict, respiratory requirements will prevail. Specific hypotheses are: (SA1[a] and [b]): phonatory laryngeal resistance will increase during hypocapnia and decrease during hypercapnia, favoring a return towards respiratory homeostasis; (SA2): amount of phonatory laryngeal resistance will in turn modulate relative homeostatic condition. Data to this effect would provide critical evidence on how respiratory and laryngeal functions may interact in phonation under conditions of respiratory abnormality. Results from this basic science study will provide a platform for future clinical research, which will explore the hypothesis that respiratory induced changes in laryngeal function may increase the risk of phonatory malfunction, will identify bio-behavioral markers for at-risk individuals, and will develop targeted evaluation and treatment protocols for them. PUBLIC HEALTH RELEVANCE: The proposed research will measure the effects of hypercapnia and hypocapnia on laryngeal airway resistance during phonation, and in turn the effects of laryngeal airway resistance changes on resulting blood gas levels. Results from the present study will guide future clinical research investigating the potential pathogenic influence of blood gas changes in affected individuals, potentially putting them at risk for laryngeal malfunction and pathology. Future research will also aim to identify bio-behavior markers for individuals at risk for respiratory-induced laryngeal pathology, and to establish targeted evaluation and treatment of at-risk individuals.